Human parainfluenza virus 3 vaccine candidates attenuated by codon-pair deoptimization are immunogenic and protective in hamsters.

Human parainfluenza virus type 3 (HPIV3) is a major pediatric respiratory pathogen lacking available vaccines or antiviral drugs. We generated live-attenuated HPIV3 vaccine candidates by codon-pair deoptimization (CPD). HPIV3 open reading frames (ORFs) encoding the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN), and polymerase (L) were modified singly or in combination to generate 12 viruses designated Min-N, Min-P, Min-M, Min-FHN, Min-L, Min-NP, Min-NPM, Min-NPL, Min-PM, Min-PFHN, Min-MFHN, and Min-PMFHN. CPD of N or L severely reduced growth in vitro and was not further evaluated. CPD of P or M was associated with increased and decreased interferon (IFN) response in vitro, respectively, but had little effect on virus replication. In Vero cells, CPD of F and HN delayed virus replication, but final titers were comparable to wild-type (wt) HPIV3. In human lung epithelial A549 cells, CPD F and HN induced a stronger IFN response, viral titers were reduced 100-fold, and the expression of F and HN proteins was significantly reduced without affecting N or P or the relative packaging of proteins into virions. Following intranasal infection in hamsters, replication in the nasal turbinates and lungs tended to be the most reduced for viruses bearing CPD F and HN, with maximum reductions of approximately 10-fold. Despite decreased in vivo replication (and lower expression of CPD F and HN in vitro), all viruses induced titers of serum HPIV3-neutralizing antibodies similar to wt and provided complete protection against HPIV3 challenge. In summary, CPD of HPIV3 yielded promising vaccine candidates suitable for further development.

The association between playing professional American football and longevity.

Recent research concludes that professional American football players (hereafter, "football players") live longer than American men in general, despite experiencing higher rates of chronic traumatic encephalopathy (CTE) and cardiovascular disease (CVD). This suggests that the longevity-enhancing benefits of playing football (e.g., physical fitness, money) outweigh the costs associated with CTE, CVD, and other longevity detriments of playing football. However, these surprising results may be the consequence of flawed research design. To investigate, we conducted two analyses. In analysis 1, we compared a) all professional American football players whose first season was 1986 or between 1988 and 1995 to b) a random sample of same-age American men observed as part of the National Health Interview Surveys in those same years selected on good health, at least 3 y of college, and not being poor. The exposure consists of playing one or more games of professional football; the outcome is risk of death within 25 y. In analysis 2, we use data on 1,365 men drafted to play in the (American) National Football League in the 1950s-906 of whom ultimately played professional football, and 459 of whom never played a game in any professional league. We estimate the association between playing football and survival through early 2023. In both analyses, we investigate differences between linemen and other position players. In contrast to most prior research, in both analyses, we find that linemen died earlier than otherwise similar men; men who played other positions died no earlier (or later).

Seismic detection of a deep mantle discontinuity within Mars by InSight.

Constraining the thermal and compositional state of the mantle is crucial for deciphering the formation and evolution of Mars. Mineral physics predicts that Mars' deep mantle is demarcated by a seismic discontinuity arising from the pressure-induced phase transformation of the mineral olivine to its higher-pressure polymorphs, making the depth of this boundary sensitive to both mantle temperature and composition. Here, we report on the seismic detection of a midmantle discontinuity using the data collected by NASA's InSight Mission to Mars that matches the expected depth and sharpness of the postolivine transition. In five teleseismic events, we observed triplicated P and S waves and constrained the depth of this discontinuity to be 1,006 [Formula: see text] 40 km by modeling the triplicated waveforms. From this depth range, we infer a mantle potential temperature of 1,605 [Formula: see text] 100 K, a result consistent with a crust that is 10 to 15 times more enriched in heat-producing elements than the underlying mantle. Our waveform fits to the data indicate a broad gradient across the boundary, implying that the Martian mantle is more enriched in iron compared to Earth. Through modeling of thermochemical evolution of Mars, we observe that only two out of the five proposed composition models are compatible with the observed boundary depth. Our geodynamic simulations suggest that the Martian mantle was relatively cold 4.5 Gyr ago (1,720 to 1,860 K) and are consistent with a present-day surface heat flow of 21 to 24 mW/m2.

Genomic variation in 3,010 diverse accessions of Asian cultivated rice.

Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within- and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.

Identification of critical points in transient electroconvection dynamics using tensor bundles.

We present and demonstrate a method to produce quantitative and qualitative descriptions of transient dynamics from empirical data, with the purpose of analyzing a novel transient discovered in liquid crystal electroconvection. By constructing a tensor bundle around an exemplar transient and creating a chart at every step aligned with the direction of propagation, we show that the Jacobian estimation problem can be reduced by a single dimension, relaxing data requirements and clarifying results. We apply this analysis to identify the onset of a boundary crisis in a predator-prey model. The resulting tensor bundle estimated from image data taken during a dynamical phase transition in a nematic liquid crystal details the behavior of the system along that trajectory, allowing topological analysis. Using this method, we quantify a saddle point in the phase space that drives the initial dynamics during a sudden increase in the driving voltage.

Structural Bias in the Completeness of Death Investigations for Sudden Unexpected Infant Deaths (SUIDs).

OBJECTIVE: To assess sudden unexpected infant death (SUID) investigations for structural inequities by race/ethnicity and geography. METHODS: The SUID Case Registry compiles data on death investigations. We analyzed cases from 2015 to 2018 (N = 3847) to examine likelihood of an incomplete death investigation, defined as missing autopsy, missing scene investigation, or missing detailed information about where and how the body was found. We also analyzed which specific components of death investigations led to the greatest number of incomplete investigations. RESULTS: Twenty-four percent of SUIDs had incomplete death investigations. Death scenes in rural places had 1.51 times the odds of incomplete death investigations (95% confidence interval [CI], 1.19-1.92) compared with urban areas. Scene investigations led by law enforcement were more likely to result in incomplete death investigations (odds ratio [OR] = 1.49; 95% CI, 1.18-1.88) than those led by medical examiners. American Indian/Alaska Native SUIDs were more likely than other racial groups to have an incomplete investigation (OR = 1.49; 95% CI, 0.92-2.42), more likely to occur in rural places ( P = .055), and more likely to be investigated by law enforcement ( P < .001). If doll reenactments had been performed, 358 additional cases would have had complete investigations, and if SUID investigation forms had been performed, 243 additional cases would have had complete investigations. American Indian/Alaska Native SUIDs were also more likely to be missing specific components of death investigations. CONCLUSION: To produce equitable public health surveillance data used in prevention efforts, it is crucial to improve SUID investigations, especially in rural areas and among American Indian/Alaska Native babies.

Potentially inappropriate medication use among older adults with lower-limb loss.

OBJECTIVE: The aim of this study was to evaluate the prevalence of, and explore factors related to, prescription of potentially inappropriate medications (PIMs) among older adults with lower-limb loss (LLL). METHODS: This was a secondary analysis of a cross-sectional dataset collected through an interdisciplinary limb loss clinic between September 2013 and November 2022. Self-report medication lists were reviewed during in-clinic face-to-face interviews and compared to the American Geriatrics Society Beers Criteria corresponding to the patient's evaluation year. RESULTS: Of 82 participants (72.9 ± 6.6 years-old; 78.0 % male), n = 41 (50.0 %) reported using one or more PIM. PIM prescription was significantly associated with presence of phantom limb pain, history of upper gastrointestinal issues, and a greater number of medications. DISCUSSION: Polypharmacy and PIM use are common among older adults with LLL. Greater attention should be paid to medications post-amputation, especially pain management medications, to minimize potential adverse side-effects.

Examining relationships between parent-reported factors and recurring ear symptoms among Aboriginal and Torres Strait Islander children.

ISSUE ADDRESSED: Aboriginal and Torres Strait Islander child ear health is complex and multiple. We examined relationships between parent-reported sociodemographic, child health, health service access factors and ear symptoms among Aboriginal and Torres Strait Islander children aged 3 to 7 years. METHODS: The Longitudinal Study of Indigenous Children is a large child cohort study with annual parent-reported data collection. Generalised linear mixed model analyses examined Wave 1 (1309 children 0-5 years; 2008) predictors of being free of parent-reported ear symptoms in both Waves 2 and 3. RESULTS: A total of 1030 (78.7%) had no reported ear symptoms in either Wave 2 or 3. In the fully adjusted model, children who had been hospitalised in the past year (aOR = 2.16; 95% CI 1.19-3.93) and those with no ear symptoms (aOR = 2.94; 95% CI, 1.59-5.46) at Wave 1 had higher odds of no ear symptoms in both the subsequent waves. There were also relationships between parent main source of income-government pension or allowance as well as parents who reported no history of their own ear symptoms and higher odds of no ear symptoms in Waves 2 and 3 after partial adjustment for sociodemographic factors. CONCLUSION: These findings suggest relationships between different sociodemographic and health factors and parent-reported ear symptoms among Aboriginal and Torres Strait Islander children that warrant further investigation. So what? Children with parent-reported ear symptoms during the early years need holistic support to prevent future ear symptoms that impact health, social and educational life trajectories.

Estimating the Long-Term Causal Effects of Attending Historically Black Colleges or Universities on Depressive Symptoms.

Racism is embedded in society, and higher education is an important structure for patterning economic and health outcomes. Historically Black Colleges and Universities (HBCUs) were founded on antiracism while predominantly White institutions (PWIs) were often founded on white supremacy. This contrast provides an opportunity to study the association between structural racism and health among Black Americans. We used the National Longitudinal Study of Adolescent to Adult Health (Add Health) to estimate the long-term causal effect of attending an HBCU (vs. PWI) on depressive symptoms among Black students in the United States from 1994-2018. While we found no overall association with attending an HBCU (vs. PWI) on depressive symptoms, we found that this association varied by baseline mental health and region, and across time. For example, among those who attended high school outside of the South, HBCU attendance was protective against depressive symptoms 7 years later, and the association was strongest for those with higher baseline depressive symptoms. We recommend equitable state and federal funding for HBCUs, and that PWIs implement and evaluate antiracist policies to improve mental health of Black students.

Resilience of Xanthoria parietina under Mars-like conditions: photosynthesis and oxidative stress response.

MAIN CONCLUSION: Xanthoria parietina survivability in Mars-like conditions was supported by water-lysis efficiency recovery and antioxidant content balancing with ROS production after 30 days of exposure. Xanthoria parietina (L.) Th. Fr. is a widespread lichen showing tolerance against air pollutants and UV-radiation. It has been tested under space-like and Mars-like conditions resulting in high recovery performances. Hereby, we aim to assess the mechanisms at the basis of the thalli resilience against multiple space stress factors. Living thalli of X. parietina were exposed to simulated Martian atmospheric conditions (Dark Mars) and UV radiation (Full Mars). Then, we monitored as vitality indicator the photosynthetic efficiency, assessed by in vivo chlorophyll emission fluorescence measurements (FM; FV/F0). The physiological defense was evaluated by analyzing the thalli antioxidant capacity. The drop of FM and FV/F0 immediately after the exposure indicated a reduction of photosynthesis. After 24 h from exposure, photosynthetic efficiency began to recover suggesting the occurrence of protective mechanisms. Antioxidant concentrations were higher during the exposure, only decreasing after 30 days. The recovery of photosynthetic efficiency in both treatments suggested a strong resilience by the photosynthetic apparatus against combined space stress factors, likely due to the boosted antioxidants at the beginning and their depletion at the end of the exposure. The overall results indicated that the production of antioxidants, along with the occurrence of photoprotection mechanisms, guarantee X. parietina survivability in Mars-like environment.

Demographic Gaps and Requirements for Participation: A Systematic Review of Clinical Trial Designs in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that disproportionally affects women, as well as Black and biracial individuals. While adalimumab remains the only therapy approved by the Food and Drug Administration for HS, many HS clinical trials for novel and re-tasked therapies are ongoing or upcoming. To optimize treatment equity, reflect the patient population, and facilitate trial participation, it is important to elucidate aspects of clinical trial protocols that may systematically exclude specific patient groups or impose hardships. OBJECTIVE: The study aimed to systematically review inclusion and exclusion criteria as well as participant demographics in HS clinical trials. METHODS: A literature search of PubMed, Embase, Cochrane Central, and Web of Science databases was conducted. Peer-reviewed publications of randomized controlled trials that were written in English and had at least 10 participants were included. Title and abstract screening and data extraction were completed by two independent reviewers, with disagreements resolved by a third. RESULTS: Twenty-three studies totaling 1,496 adult participants met the inclusion criteria. Race and ethnicity were not reported in 473/1,496 (31.6%) and 1,420/1,496 (94.9%) trial participants, respectively. Trial participants were predominantly white (811/1,023, 79.3%) and female (1,057/1,457, 72.5%). The median of each study's average age was 35.7 years (IQR 33.5-38.0), and 17/23 (73.9%) trials excluded pediatric patients. Nearly all participants had Hurley Stage II (499/958, 52.0%) or Hurley Stage III (385/958, 40.2%) disease. Many trials excluded patients who were pregnant (19/23, 82.6%) and breastfeeding (13/23, 56.5%), or who had HS that was "too severe" (8/23, 34.8%) or "too mild" (16/23, 70.0%). Frequently, trial protocols required prolonged washout periods from HS therapies, relatively long duration in the study's placebo arm, and prohibited concurrent analgesic use. CONCLUSIONS: This systematic review of 23 HS clinical trials totaling 1,496 participants identified substantial hardships imposed by trial participation, high rates of missing race and ethnicity data, and low representation of key patient groups, including those who identify as Black. Future trials with pragmatic study designs, broader inclusion criteria, and study sites in diverse communities may alleviate burdens of trial participation and improve enrollment of diverse patient groups.

Transient power dynamics in nematic electroconvection.

We have observed the transient dynamics in nematic electroconvection during a sudden change in the driving voltage. The steady state dynamics of nematic electroconvection during a constant driving voltage are well characterized examples of spatiotemporal chaos, and thus are useful for the study of chaotic transients. For a set of starting conditions, we were able to show that the system can enter a long-lived transient state with a larger power dissipation rate. This transient state decays through the skew varicose instabilities into steady state defect turbulence. We observed the onset of both Eckhaus and skew varicose instabilities, interpret this transition in the framework of dynamical crisis, and quantify the transition through the evolution of the information entropy in the images as well as the power dissipated by the sample. We identify this long-lived but transient state as originating from the structure of the convective rolls in the initial state and hypothesize that the exploitation of transient states such as these may occur in natural systems and could be leveraged for industrial processing.

Consumers' longitudinal health information needs and seeking: a scoping review.

Needing and seeking health information often is a longitudinal everyday life information behavior that involves the use of technology. However, no reviews of consumers' longitudinal health information needs (HIN) and health information-seeking (HIS) behavior have been conducted. We performed a scoping review to address this gap. Specifically, we surveyed the characteristics, timeline construction and research findings of studies investigating consumers' longitudinal HIN and HIS. Initial searches were conducted in November 2019 and updated in July 2022. A total of 128 papers were identified, reviewed and analyzed using content and thematic analyses. Results showed that most papers were quantitative, conducted in the USA, related to cancer, conducted during the diagnosis and treatment phases, and followed preset time intervals. Findings concerning the development patterns of consumers' HIN degrees and HIS effort were mixed (i.e. increasing, decreasing or being consistent over time). They seemed to be shaped by factors such as health conditions, data collection methods and the length of data collection. Consumers' use of sources changes depending on health status and source accessibility; their medical terminologies seem to expand over time. HIS has a strong emotional dimension which may lead to adaptive or maladaptive information behaviors (e.g. information avoidance). Overall, the results revealed a lack of understanding of HIN and HIS from a longitudinal perspective, particularly along health condition progression and coping trajectories. There is also a lack of understanding of the role of technologies in the longitudinal HIS process.

Contemporary perspectives on the ecological impacts of invasive freshwater fishes.

Introductions of non-native freshwater fish continue to increase globally, although only a small proportion of these introductions will result in an invasion. These invasive populations can cause ecological impacts in the receiving ecosystem through processes including increased competition and predation pressure, genetic introgression and the transmission of non-native pathogens. Definitions of ecological impact emphasize that shifts in the strength of these processes are insufficient for characterizing impact alone and, instead, must be associated with a quantifiable decline of biological and/or genetic diversity and lead to a measurable loss of diversity or change in ecosystem functioning. Assessments of ecological impact should thus consider the multiple processes and effects that potentially occur from invasive fish populations where, for example, impacts of invasive common carp Cyprinus carpio populations are through a combination of bottom-up and top-down processes that, in entirety, cause shifts in lake stable states and decreased species richness and/or abundances in the biotic communities. Such far-reaching ecological impacts also align to contemporary definitions of ecosystem collapse, given they involve substantial and persistent declines in biodiversity and ecosystem functions that cannot be recovered unaided. Thus, while not all introduced freshwater fishes will become invasive, those species that do develop invasive populations can cause substantial ecological impacts, where some of the impacts on biodiversity and ecosystem functioning might be sufficiently harmful to be considered as contributing to ecosystem collapse.

Effects of preservation by ethanol on δ13 C and δ15 N of three tissues of the critically endangered European eel Anguilla anguilla.

The temporal effects of ethanol preservation on the δ13 C and δ15 N values of tissues excised from European eel Anguilla anguilla were assessed. Preservation significantly enriched 13 C values of fin and mucus but not dorsal muscle. The 13 C enrichment occurred in the initial 15 days of preservation and was independent of initial eel mass. Tissue preservation effects on δ15 N values were negligible. These tissue-specific isotopic shifts should be considered when ethanol-preserved eel samples are used.

Early life exposure to cigarette smoking and adult and old-age male mortality: Evidence from linked US full-count census and mortality data.

BACKGROUND: Smoking is a leading cause of premature death across contemporary developed nations, but few longitudinal individual-level studies have examined the long-term health consequences of exposure to smoking. OBJECTIVE: We examine the effect of fetal and infant exposure to exogenous variation in smoking, brought about by state-level cigarette taxation, on adulthood and old-age mortality (ages 55-73) among cohorts of boys born in the United States during the 1920s and 1930s. METHODS: We use state-of-the-art methods of record linkage to match 1930 and 1940 US full-count census records to death records, identifying early life exposure to the implementation of state-level cigarette taxes through contemporary sources. We examine a population of 2.4 million boys, estimating age at death by means of OLS regression, with post-stratification weights to account for linking selectivity. RESULTS: Fetal or infant exposure to the implementation of state cigarette taxation delayed mortality by about two months. Analyses further indicate heterogenous effects that are consistent with theoretical expectations; the largest benefits are enjoyed by individuals with parents who would have been affected most by the tax implementation. CONCLUSIONS: Despite living in an era of continuously increasing cigarette consumption, cohorts exposed to a reduction in cigarette smoking during early life enjoyed a later age at death. While it is not possible to comprehensively assess the treatment effect on the treated, the magnitude of the effect should not be underestimated, as it is larger than the difference between having parents belonging to the highest and lowest socioeconomic groups. CONTRIBUTION: The study provides the first estimates of long-run health effects from early life exposure to cigarette smoking.

Post-amputation pain: Comparing pain presentations between adults with and without increased amputated-region sensitivity.

OBJECTIVE: Among adults with persistent post-amputation pain, increased amputated-region pain sensitivity may reflect peripheral sensitization or indicate underlying central sensitization. To determine whether underlying central sensitization may contribute to increased pain sensitivity in this population, this study compared clinical signs and symptoms associated with central sensitization between adults with post-amputation pain who demonstrate or lack increased amputated-region sensitivity (as compared to reference data). DESIGN: Cross-sectional. SUBJECTS: Ninety-nine adults (60 with a unilateral, transtibial amputation and post-amputation pain, 39 pain-free controls with intact limbs). METHODS: Participants underwent pain-pressure threshold testing of amputated-region and secondary (non-amputated region) sites and completed outcome measures assessing central sensitization symptoms (Patient-Reported Outcomes Measurement Information System® pain intensity and interference domains, Central Sensitization Inventory). Among the full sample, the presence and frequency of specific central sensitization symptoms were evaluated. Participants with post-amputation pain were then grouped based on whether normalized, amputated-region pain-pressure thresholds fell below (i.e., sensitive) or above (i.e., non-sensitive) the 25th percentile of sex-specific reference data. Between-group differences in normalized secondary-site sensitivity were evaluated using a multivariate analysis of variance; central sensitization symptom scores were compared using a Kruskal-Wallis test. RESULTS: Noteworthy symptoms associated with central sensitization (e.g., fatigue, sleep disturbance, cognitive difficulty) were reported by 33%-62% of participants. Secondary-site pain sensitivity was greater among individuals with increased amputated-region sensitivity (n = 24) compared to peers without increased amputated-region sensitivity ([n = 36], mean difference > 1.33 standard deviation [SD], p < 0.001). Central sensitization symptom scores, however, were similar between groups (p > 0.187). CONCLUSIONS: Participants with increased amputated-region sensitivity demonstrate generalized, secondary-site pain hypersensitivity, potentially indicating underlying central sensitization. Central sensitization symptom scores, however, were similar between groups, suggesting differences in physiological pain sensitivity may not manifest in subjective post-amputation pain descriptions.

Childhood Growth and Socioeconomic Outcomes in Early Adulthood Evidence from the Inter-War United States.

Childhood malnutrition and its later life effects were important concerns in European and North American social policy in the early twentieth century. However, there have been few studies of the long-term socioeconomic consequences of malnutrition in childhood. We use a unique longitudinal dataset to provide credible causal estimates of the effects of childhood nutrition on early-adult educational and employment outcomes. Our dataset includes 2,499 children in Saint Paul, Minnesota who were weighed and measured in a national children's health survey in 1918/1919 at 0-6 years of age. We observe those same people in the 1920, 1930 and 1940 U.S. censuses allowing us to measure childhood socioeconomic status (1920), adolescent school attendance (1930) and early-adult wages, and employment and educational attainment (1940). Examining variation between biological siblings, we are able to obtain credibly causal estimates of the relationship between childhood stature and weight and later life outcomes, largely canceling out the bias otherwise resulting from their joint correlation with genes and socioeconomic background. Because the initial survey located children within households, we identify the effect of differences in early childhood nutrition from differences between male siblings. Consistent with contemporary evidence from developing countries we find that being taller and heavier in early childhood is associated with better educational and labor market outcomes. Identifying all effects within families to control for socioeconomic background and family structure we find a standard deviation increase in BMI in early childhood was associated with a 3% increase in weekly earnings and that boys who were heavier for their age at the initial survey were 10% less likely to be unemployed in 1940. Taken together, these results confirm the importance of investments in early life health for later-life outcomes.

Hippo signalling during development.

The Hippo signalling pathway and its transcriptional co-activator targets Yorkie/YAP/TAZ first came to attention because of their role in tissue growth control. Over the past 15 years, it has become clear that, like other developmental pathways (e.g. the Wnt, Hedgehog and TGFß pathways), Hippo signalling is a 'jack of all trades' that is reiteratively used to mediate a range of cellular decision-making processes from proliferation, death and morphogenesis to cell fate determination. Here, and in the accompanying poster, we briefly outline the core pathway and its regulation, and describe the breadth of its roles in animal development.

Transcriptional analysis identifies potential novel biomarkers associated with successful ex-vivo perfusion of human donor lungs.

BACKGROUND: Transplantation is an effective treatment for end-stage lung disease, but the donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of extended criteria organs enables functional assessment to facilitate clinical decision-making around utilization, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remain to be determined. METHODS: We used RNA sequencing of lung tissue to delineate changes in gene expression occurring in 10 donor lungs undergoing EVLP and compare lungs that were deemed non-transplantable (n = 4) to those deemed transplantable (n = 6) following perfusion. RESULTS: We found that lungs deemed unsuitable for transplantation had increased induction of innate immune pathways and lower expression of oxidative phosphorylation related genes. Furthermore, the expression of SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes was significantly decreased in non-transplantable lungs, while CHIT-1 was increased. Using a larger validation cohort (n = 17), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable from non-transplantable lungs (AUC .81). CONCLUSIONS: Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may be amenable to therapeutic intervention during EVLPAQ6.